Impact of SARS-CoV-2 (COVID-19) Pandemic on Characteristics and Management of Uveal Melanoma in National Referral Center in Poland (preprint)

Background: to analyze the impact of COVID-19 pandemic on characteristics and management of uveal melanoma (UM) in National Referral Center in Poland. Materials and Methods: the retrospective analysis of 1336 patients who were newly diagnosed with UM at Department of Ophthalmology and Ophthalmic Oncology, Jagiellonian University Collegium Medicum Krakow, Poland between January 1, 2018 and December 31, 2021. The demographic and clinical data were compiled including localization, size and treatment methods of tumors. Results: In total, 728 patients with UM were included before COVID-19 pandemic in years 2018-2019 and 608 were included during COVID-19 pandemic in years 2020-2021. Fixed-base dynamics indicators for the incidence of uveal melanoma (base year 2018) in the national referral center in Poland were 80.22% and 86.81% in year 2020 and 2021, respectively. UMs were statistically significantly larger and more frequently localized anterior to the equator of the eye globe in year 2021 than in year 2018 (Chi^2 Pearson test p= 0.0001 and p= 0.0077, respectively). The rate of patients treated with enucleation increased from 15.94% in year 2018 to 26.90% in year 2021 (Chi^2 Pearson test p=0.0005). Conclusions: statistically significant differences were found in the management of uveal melanoma in National Referral Center in Poland during COVID-19 pandemic with tumors being larger, more frequently localized anterior to the equator of the eye globe and more often enucleated.

Development of an engineered extracellular vesicles-based vaccine platform for combined delivery of mRNA and protein to induce functional immunity (preprint)

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs to contain ovalbumin mRNA and protein (EVOvaM+P) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice with established melanoma tumors resulted in tumor regression associated with effective humoral and adaptive immune responses. As a second example, we generated engineered EVs, natural nanoparticle carriers shed by all cells, that contain mRNA and protein Spike (S) protein to serve as a combined mRNA and protein vaccine (EVSpikeM+P vaccine) against SARS-CoV-2 infection. EVSpikeM+P vaccine administration in mice and baboons elicited robust production of neutralizing IgG antibodies against RBD (receptor binding domain) of S protein and S protein specific T cell responses. Our proof-of-concept study describes a new platform with an ability for rapid development of combination mRNA and protein vaccines employing EVs for deployment against cancer and other diseases.

The effect of COVID-19 disease on patients diagnosed with skin cancer in the dermatology clinic (preprint)

Objective: We aimed to define the impact of the pandemic on patients presenting to dermatology clinic with skin cancer. Methods: In our study, the characteristics of patients who attended our dermatology clinic before six months and after six months of March 11, 2020, and whose biopsies diagnosed as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) were evaluated and compared regarding before and after COVID-19 pandemic Results: Patients with BCC attending to the dermatology clinic were found to be younger in the pandemic period (p<0.05). Gender, duration of skin tumors, primary lesions, and their locations were found to be not statistically significant (p>0.05). Conclusion:Patients with suspicious skin lesions could be encouraged to visit a hospital with appropriate COVID-19 protection. Alternatively, teledermatology could be used to evaluate whether the lesions should be excised or biopsied.

Comparison of chest radiological findings between coronavirus disease 2019 pneumonia and anti-melanoma differentiation-associated gene 5 antibody- positive interstitial pneumonia by artificial intelligence-based quantitative computed tomography image analysis (preprint)

Background Coronavirus disease 2019 (COVID-19) pneumonia and anti-melanoma differentiation-associated gene 5 antibody-positive interstitial pneumonia (MDA5-IP) share many similarities; however, the treatment and management of the two diseases are different. In the early stages of developing a treatment plan, it is crucial to distinguish between the two diseases. This study was conducted to compare the radiological findings between COVID-19 pneumonia and MDA5-IP.Methods We recruited patients with COVID-19 pneumonia between January and June 2020. The control group comprised patients with MDA5-IP admitted between April 2013 and December 2019. Patients with thin-slice computed tomography (CT) images within 2 days of admission were enrolled. The CT images were analyzed using an artificial intelligence-based quantitative CT software program. Radiological findings were classified as faint ground-glass opacity (GGO), GGO, reticulation, consolidation, honeycombing, nodules, hyperlucency, or interlobular septum. The volumes of these radiological findings were compared between the two groups. A classification and regression tree algorithm was used to develop a prediction model to stratify the risk of COVID-19 pneumonia.Results We enrolled 72 and 15 patients in the COVID-19 pneumonia and MDA5-IP group, respectively. Faint GGO and consolidations were observed more extensively in patients with MDA5-IP. The prediction model was developed at cut-off values of faint GGO, < 30%; GGO, ≥ 10%, and consolidation < 1%. This prediction model contributed to changing post-test probability in 26% of cases.Conclusion The COVID-19 group showed fewer faint GGO and consolidation volumes than the MDA5-IP group. We developed a predictive model to stratify the risk of COVID-19 pneumonia.

IFIH1 loss-of-function predisposes to inflammatory and SARS-CoV-2-related infectious diseases (preprint)

The IFIH1 gene, encoding melanoma differentiation-associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation linking it to weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain-of-function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi-Goutieres and Singleton-Merten syndromes, while biallelic loss of this gene causes immunodeficiency. In this study, nine patients suffering from different cases of recurrent infections, inflammatory diseases, severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C) were identified with putative loss-of-function IFIH1 variants by whole exome sequencing. All patients revealed signs of lymphopenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin, and IL-6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID-19, or MIS-C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS-C. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss-of-function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS-CoV-2 related disorders.

Not Waiting to Progress; How the COVID-19 Pandemic Nudged Neoadjuvant Therapy for Stage III Locally Advanced Melanoma Patients.

Background: Early-phase neoadjuvant trials have demonstrated promising results in the utility of upfront immunotherapy in locally advanced stage III melanoma and unresected nodal disease. Secondary to these results and the COVID-19 pandemic, this patient population, traditionally managed through surgical resection and adjuvant immunotherapy, received a novel treatment strategy of neoadjuvant therapy (NAT). Methods: Patients with node-positive disease, who faced surgical delays secondary to COVID-19, were treated with NAT, followed by surgery. Demographic, tumour, treatment and response data were collected through a retrospective chart review. Biopsy specimens were analysed prior to the initiation of NAT, and therapy response was analysed following surgical resection. NAT tolerability was recorded. Results: Six patients were included in this case series; four were treated with nivolumab alone, one with ipilimumab and nivolumab and one with dabrafenib and trametinib. Twenty-two incidents of adverse events were reported, with the majority (90.9%) being classified as grade one or two. All patients underwent surgical resection: three out of six patients following two NAT cycles, two following three cycles and one following six cycles. Surgically resected samples were histopathologically evaluated for the presence of disease. Five out of six patients (83%) had ≤1 positive lymph node. One patient showed extracapsular extension. Four patients demonstrated complete pathological response; two had persisting viable tumour cells. Conclusions: In this case series, we outlined how in response to surgical delays secondary to the COVID-19 pandemic, NAT was successfully applied to achieve promising treatment response in patients with locally advanced stage III melanoma.

A call for implementing augmented intelligence in pediatric dermatology.

Augmented intelligence (AI), the combination of artificial based intelligence with human intelligence from a practitioner, has become an increased focus of clinical interest in the field of dermatology. Technological advancements have led to the development of deep-learning based models to accurately diagnose complex dermatological diseases such as melanoma in adult datasets. Models for pediatric dermatology remain scarce, but recent studies have shown applications in the diagnoses of facial infantile hemangiomas and X-linked hypohidrotic ectodermal dysplasia; however, we see unmet needs in other complex clinical scenarios and rare diseases, such as diagnosing squamous cell carcinoma in patients with epidermolysis bullosa. Given the still limited number of pediatric dermatologists, especially in rural areas, AI has the potential to help overcome health disparities by helping primary care physicians treat or triage patients.

CD71+ erythroid cells suppress T-cell effector functions and predict immunotherapy outcomes in patients with virus-associated solid tumors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. However, only a portion of patients respond to such treatments. Therefore, it remains a prevailing clinical need to identify factors associated with acquired resistance or lack of response to ICIs. We hypothesized that the immunosuppressive CD71+ erythroid cells (CECs) within the tumor and/or distant 'out-of-field' may impair antitumor response. METHODS: We studied 38 patients with cancer through a phase II clinical trial investigating the effects of oral valproate combined with avelumab (anti-programmed death-ligand 1 (PD-L1)) in virus-associated solid tumors (VASTs). We quantified the frequency/functionality of CECs in blood and biopsies of patients. Also, we established an animal model of melanoma (B16-F10) to investigate the possible effects of erythropoietin (EPO) treatment on anti-PD-L1 therapy. RESULTS: We found a substantial expansion of CECs in the blood of patients with VAST compared with healthy controls. We noted that the frequency of CECs in circulation was significantly higher at the baseline and throughout the study in non-responders versus responders to PD-L1 therapy. Moreover, we observed that CECs in a dose-dependent manner suppress effector functions of autologous T cells in vitro. The subpopulation of CD45+CECs appears to have a more robust immunosuppressive property compared with their CD45- counterparts. This was illustrated by a stronger expression of reactive oxygen species, PD-L1/PD-L2, and V-domain Ig suppressor of T-cell activation in this subpopulation. Lastly, we found a higher frequency of CECs in the blood circulation at the later cancer stage and their abundance was associated with anemia, and a poor response to immunotherapy. Finally, we report the expansion of CECs in the spleen and tumor microenvironment of mice with melanoma. We found that although CECs in tumor-bearing mice secret artemin, this was not the case for VAST-derived CECs in humans. Notably, our results imply that EPO, a frequently used drug for anemia treatment in patients with cancer, may promote the generation of CECs and subsequently abrogates the therapeutic effects of ICIs (eg, anti-PD-L1). CONCLUSIONS: Our results demonstrate that anemia by the expansion of CECs may enhance cancer progression. Notably, measuring the frequency of CECs may serve as a valuable biomarker to predict immunotherapy outcomes.

Using temporal heatmaps to identify worthwhile articles on immune checkpoint blockade for melanoma (ICBM) in Mainland China, Hong Kong, and Taiwan since 2000: A bibliometric analysis.

BACKGROUND: Melanoma is a life-threatening form of skin cancer. Due to its remarkable effectiveness, the immune checkpoint blockade is widely used to treat melanoma (ICBM). No research has been conducted on ICBM for identifying the most readable articles. A bibliometric analysis of 100 top-cited ICBM (T100ICBM) in recent decades is required to highlight articles worth reading. METHODS: Based on the Web of Science Core Collection, we summarized the articles on ICBM published in each year from 2000 to 2022, with first authors from Mainland China, Hong Kong, and Taiwan (CHT). Using the CJAL score, data extraction and visualization of the distribution of ICBM publications were conducted on 2718, and 100 top-cited articles, respectively. We used the temporal heatmap to identify the most readable articles. Four descriptive, diagnostic, predictive, and prescriptive analytics (called DDPP model) were applied to describe the features of T100ICBM articles. The absolute advantage coefficient was used to determine the dominance extent of the most influential region, institute, department, and author. RESULTS: A total of 2718 publications was included after removing first or corresponding authors who were not affiliated with CHT. Publications by year showed a sharp increase from 2014 onward and either peaked in 2022 or have not yet peaked. It was evident that there was a large difference between the number of publications in provinces/metropolitan cities/regions on CHT. Beijing, Sichuan University, Oncology, and Guo Jun from Beijing are the most prolific and influential region, institute, department, and author. When comparing research achievements to the next productive authors based on the CJAL score, only Dr Jun has a medium effect of dominance (=0.60). On the basis of their consecutive growth in citations over the past 4 years, 20 T100ICBM articles were recommended for readers. CONCLUSION: The field of ICBM is growing rapidly, and Beijing and Sichuan University are taking the lead in CHT. Furthermore, the study provides references for worth-reading articles using the temporal heatmap. Future research hot spots may focus on these 4 themes of immunotherapy, melanoma, metastatic melanoma, regulatory T cells, cells, and activation, which may pave the way for additional study.

mRNA melanoma vaccine revolution spurred by the COVID-19 pandemic.

The advent of mRNA vaccines represents a significant advance in the field of vaccinology. While several vaccine approaches (mRNA, DNA, recombinant protein, and viral-vectored vaccines) had been investigated at the start of the COVID-19 pandemic, mRNA vaccines quickly gained popularity due to superior immunogenicity at a low dose, strong safety/tolerability profiles, and the possibility of rapid vaccine mass manufacturing and deployment to rural regions. In addition to inducing protective neutralizing antibody responses, mRNA vaccines can also elicit high-magnitude cytotoxic T-cell responses comparable to natural viral infections; thereby, drawing significant interest from cancer immunotherapy experts. This mini-review will highlight key developmental milestones and lessons we have learned from mRNA vaccines during the COVID-19 pandemic, with a specific emphasis on clinical trial data gathered so far for mRNA vaccines against melanoma and other forms of cancer.

Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.

INTRODUCTION: The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI). METHODS: Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR). RESULTS: Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20). CONCLUSION: PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.

Impact of the COVID-19 pandemic on melanoma diagnosis and presentation: a `review.

The ongoing challenges posed by COVID-19 are concerning for their impact on successful detection and recognition of melanoma as total body skin examinations and skin biopsies are critical for identifying early-stage melanoma and intervening before progression to metastatic disease. A comprehensive electronic search of PubMed/MEDLINE was conducted on or before August 1, 2022, using the search terms ("skin" AND "COVID-19"), (["skin cancer" AND "COVID-19"] OR ["skin cancer" AND "coronavirus"]), (["melanoma" AND "COVID-19"] OR ["melanoma" AND "coronavirus"]), ("dermatology" AND "COVID-19"), and ("cutaneous" AND "COVID-19"). Eight articles representing Belgium, Chile, France, Germany, Spain, the United Kingdom, and the United States were included. Four articles analyzed changes in the proportion of in situ melanoma at diagnosis and consistently reported decreases, with an overall decrease ranging from 7.6 to 40.4%. Five studies analyzed changes in the proportion of melanoma diagnoses by staging, but no clear changes in staging patterns were observed. Five studies analyzed changes in the mean Breslow thickness of melanoma diagnoses and consistently reported increases, with an overall increase ranging from 4.0 to 38%. Disruptions to proper diagnosis and treatment of melanoma are creating undue morbidity, mortality, and healthcare costs as the pandemic continues. Continued research with improved, centralized data collection is needed to better address the COVID-19 pandemic's ongoing challenge to appropriate detection and treatment of melanoma.

Impact of COVID-19 on a rare disease (uveal melanoma) in a national reference unit of intraocular tumors in Spain.

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on the diagnosis and management of uveal melanoma (a tumour included in the Orphanet catalogue of rare diseases) in a Spanish national reference unit for intraocular tumours during the first year of the pandemic. METHOD: An observational retrospective study of patients with uveal melanoma in the National Reference Unit for Adult Intraocular Tumors of the Hospital Clínico Universitario de Valladolid (Spain) was performed, analysing the pre- and post-COVID-19 periods: from March 15, 2019 to March 15, 2020 and from March 16, 2020 to March 16, 2021. Demographic data, diagnostic delay, tumour size, extraocular extension, treatment and evolution were collected. A multivariable logistic regression model was used to identify factors that were associated with the variable: enucleation. RESULTS: Eighty-two patients with uveal melanoma were included, of which 42 (51.21%) belonged to the pre-COVID-19 period and 40(40.78%) to the post-COVID-19 period. An increase in tumour size at diagnosis and in the number of enucleations was observed during the post-COVID-19 period (p < 0.05). Multivariable logistic regression demonstrated that both medium-large tumour size and patients diagnosed in the post-COVID-19 period were independently related to an increased risk of enucleation (OR 250, 95%CI, 27.69-2256.37; p < 0.01 and OR 10; 95%CI, 1.10-90.25; p = 0.04, respectively). CONCLUSIONS: The increase in tumour size observed in uveal melanomas diagnosed during the first year of the COVID-19 pandemic may have favored the increase in the number of enucleations performed during that period.

Adipocytes Encapsulating Telratolimod Recruit and Polarize Tumor-Associated Macrophages for Cancer Immunotherapy.

Tumor-associated adipocytes (TAAs) recruit monocytes and promote their differentiation into tumor-associated macrophages (TAMs) that support tumor development. Here, TAAs are engineered to promote the polarization of TAMs to the tumor suppressive M1 phenotype. Telratolimod, a toll-like receptor 7/8 agonist, is loaded into the lipid droplets of adipocytes to be released at the tumor site upon tumor cell-triggered lipolysis. Locally administered drug-loaded adipocytes increased tumor suppressive M1 macrophages in both primary and distant tumors and suppressed tumor growth in a melanoma model. Furthermore, drug-loaded adipocytes improved CD8+ T cell-mediated immune responses within the tumor microenvironment and favored dendritic cell maturation in the tumor draining lymph nodes.

Apatinib combined with camrelizumab in advanced acral melanoma patients: An open-label, single-arm phase 2 trial.

BACKGROUND: At present, immune monotherapy and combination therapy has not shown satisfactory effects on acral melanoma, and still no standard treatment is available for advanced acral melanoma. Here, a phase II trial was performed to explore the safety and efficacy of apatinib combined with camrelizumab in advanced acral melanoma patients as first-line therapy (NCT03955354). METHODS: Patients with pathologically confirmed, locally unresectable or metastatic treatment native acral melanoma received 250 mg apatinib once daily and camrelizumab 200 mg once every two weeks intravenously every 28-day cycle. The primary end-point was objective response rate and the secondary end-points were disease control rate, overall survival, progression-free survival and safety. RESULTS: Thirty patients were recruited between January 2015 and January 2022. Among them, 21 (70.0%) had stage IV, and a median tumour burden was 50 mm (range: 11-187). Objective response rate was 24.1%, and 7 of 29 patients had an anti-tumour response, including partial response (n = 5) and complete response (n = 2). Disease control rate was 82.8%, median progression-free survival was 7.39 months (confidence interval: 3.65-9.92), and median overall survival was 13.4 months (confidence interval: 1.9-25.0). Grade 3-4 treatment-related toxicity (grade 3 50.5%; grade 4 3.3%) included transaminase elevations, proteinuria, leukocytopenia, vomiting, diarrhea and drug-induced liver injury. No treatment-related mortality occurred. The mutations of TTN, MUC16, VPS13D, ALPK2 and SCUBE1 showed significant alterations with survival outcome. CONCLUSIONS: Apatinib combined with camrelizumab showed manageable safety profile and reasonable anti-tumour activity in advanced acral melanoma patients as first-line therapy.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Did COVID-19 lockdown delay actually worsen melanoma prognosis?

BACKGROUND: The COVID-19 lockdown possibly meant a delay in the diagnosis and treatment of melanoma and therefore, worsening its prognosis. This unique situation of diagnosis deferral is an exceptional opportunity to investigate melanoma biology. OBJECTIVES: To evaluate the immediate and mid-term impact of diagnosis delay on melanoma. METHODS: A retrospective observational study of melanoma diagnosed between March 14th 2019 and March 13th 2021. We compared the characteristics of melanomas diagnosed during the first 6-month period after the lockdown instauration and a second period after recovery of normal activity with the same periods of the previous year, respectively. RESULTS: A total of 119 melanomas were diagnosed. There were no differences in age, sex, incidence, location, presence of ulceration or mitoses, and in situ/invasive melanoma rate (p>0.05). After the recovery of the normal activity, Breslow thickness increased in comparison with the previous year (2.4 vs 1.9mm, p<0.05) resulting in a significant upstaging according to the AJCC 8th ed. (p<0.05). STUDY LIMITATIONS: The main limitation is that this is a single-center study. CONCLUSIONS: The COVID-19 lockdown implied a diagnosis delay leading to a mid-term increase in Breslow thickness and an upstaging of invasive melanomas. However, the detection deferral did not result in a higher progression of in situ to invasive melanoma, in our sample.

Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.

The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.

Malignant Melanoma Arising in a Prolific Nevus Sebaceus With Colonization of Trichoblastoma.

ABSTRACT: Nevus sebaceus (NS) is a cutaneous hamartoma typically found on the head and neck, with a prevalence of 0.3% in newborns. Most NS are quiescent; however, benign and malignant lesions have been reported to arise within these nevi. Malignant transformation is not common but mainly includes basal cell carcinoma and squamous cell carcinoma. Malignant melanoma arising in NS is exceedingly rare, with only 2 previously documented cases. In this article, we report the first case of malignant melanoma arising in a NS in a 68-year-old man in the United States.